Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

• Published in: PloS one Vol. 14; no. 12; p. e0226481
• Main Authors: Clarke, Tomas, Jamieson, Jessie D, Malone, Patrick, Rayhan, Rakib U, Washington, Stuart, VanMeter, John W, Baraniuk, James N
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2019; Public Library of Science (PLoS)
• Subjects: Adult; Atrophy; Attention; Attention task; Basal ganglia; Biology and Life Sciences; Brain; Brain stem; Brain Stem - diagnostic imaging; Brain Stem - pathology; Cardiac arrhythmia; Chronic pain; Cognition & reasoning; Cognitive ability; Cognitive disorders; Cognitive tasks; Computer and Information Sciences; Connectome; Correlation; Cortex (cingulate); Cortex (frontal); Epidemiology; Executive function; Exhaustion; Fatigue; Female; Ganglia; Gastrointestinal diseases; Gene expression; Gulf War; Gulf War syndrome; Heart Rate; Humans; Hypotheses; Illnesses; Immunology; Magnetic resonance; Magnetic Resonance Imaging; Male; Medicine and Health Sciences; Memory; Middle Aged; Military personnel; Modules; Neural networks; NMR; Nodes; Nuclear magnetic resonance; Pain; Pattern recognition; Persian Gulf Syndrome - diagnostic imaging; Persian Gulf Syndrome - pathology; Persian Gulf Syndrome - physiopathology; Persian Gulf War; Phenotype; Phenotypes; Physical Exertion; Posture; Prefrontal cortex; Rheumatology; Sleep; Social Sciences; Tachycardia; Veterans; Veterans - psychology; War; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226481

One quarter of veterans returning from the 1990-1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task ("see a letter, push a button") performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia-anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction.